This program project seeks to improve the diagnosis and treatment of patients with cancer through a better understanding of cancer biology, improvements in cancer classification and diagnosis, and identification of new molecular targets and strategies for treatment. The multidisciplinary program emphasizes exploits systematic, highly parallel approaches to the molecular characterization of human cancer, particularly the use of DNA microarrays and tissue microarrays to profile gene and protein expression patterns. The central hypothesis is that any clinically important differences among cancers, or between cancers and their normal cellular counterparts, will be accompanied by a corresponding difference in gene expression programs. The research projects in this program include (1) a study aimed at identifying and characterizing the cells in the microenvironment of cancer tissues and their interactions, and; a systematic study of the cellular responses to molecular signals important in cancer; (2) a study of prostate cancer aimed at understanding the clinical implications and the biological basis of three distinct molecular subtypes of prostate cancer discovered in previous work, relating patterns of gene expression to chromosomal alterations, and developing and evaluating new prognostic markers; (3) a study of global gene expression and molecular diversity, in small, early stage breast cancers and a critical evaluation of the performance of gene-expression based prognostic criteria in predicting the clinical course of these early cancers; and (4) a large systematic investigation of the gene expression patterns in soft-tissue sarcomas, aimed at development of new molecular markers for diagnosis and new molecular targets for therapy of these cancers, and at improving our understanding of the stromal proliferation that is a common features of carcinomas. The program is supported by an administrative core (Core C) that will support, organize and provide supervision of the projects, and two research cores - a DNA microarray informatics and biostatistics core (Core A) that will support a microarray database for archiving, analysis and public distribution of data from this project and provide expert consultation and support for data analysis; and a tissue microarray core (Core B) that will produce and provide tissue microarrays, support for immunostaining and in situ hybridization, support for histopathological interpretation, and automated image analysis and image database support. [unreadable] [unreadable]